One year of SARS-CoV-2 circulation in the Nouvelle-Aquitaine region, February 2021-2022, France.

Background: Since 2021, 3 variants of concern (VOC) have spread to France, causing successive epidemic waves. Objectives: To describe the features of Alpha, Delta and Omicron VOC circulation in the Nouvelle-Aquitaine region, France, between February 2021 and February 2022. Study design: Data from the three university hospitals (UH) of Nouvelle-Aquitaine were used to describe regional SARS-CoV-2 circulation (RT-PCR positive rates and identified VOC) as well as its consequences (total number of hospitalizations and admissions in intensive care unit). They were analyzed according to the predominant variant and compared with national data. Results: A total of 611,106 SARS-CoV-2 RT-PCR tests were performed in the 3 Nouvelle-Aquitaine UH during the study period. The 37,750 positive samples were analyzed by variant-specific RT-PCR or whole-genome sequencing. In 2021, Alpha VOC was detected from week 5 until week 35. Delta became the most prevalent variant (77.3%) in week 26, reaching 100% in week 35. It was replaced by Omicron, which was initially detected week 48, represented 77% of positive samples in week 52 and was still predominant in February 2022. The RT-PCR positive rates were 4.3, 4.2, and 21.9% during the Alpha, Delta and Omicron waves, respectively. The ratio between intensive care unit admissions and total hospitalizations was lower during the Omicron wave than during the two previous waves due to the Alpha and Delta variants. Conclusion: This study highlighted the need for strong regional cooperation to achieve effective SARS-CoV-2 epidemiological surveillance, in close association with the public health authorities.

Outcome of febrile neutropenic patients treated for bacteriuria in hematology.

INTRODUCTION: Positive urine sample is a frequent finding in post-chemotherapy febrile neutropenia (FN) and can lead to prolonged antibiotic therapy. The aim of this study was to assess the outcome of bacteriuria episodes in FN patients receiving targeted antibiotic therapy. MATERIALS AND METHODS: A multi-centric retrospective study was conducted over a four-year period (2014-2019) on systematic urinalysis. All consecutive first bacteriuria episodes (≤ 2 bacteria with at least ≥ 103 CFU/mL) during FN in hospitalized adult patients for hematological malignancies were included. Relapse and recurrence were defined by fever or urinary tract symptoms (UTS) with the same bacterial subspecies in urine occurring ≤ 7 days and ≤ 30 days, respectively, after antibiotic discontinuation. Mortality rate was determined at 30 days. Targeted antibiotic therapy ≤ 10 days for women and ≤ 14 for men was considered as short course. RESULTS: Among 97 patients, 105 bacteriuria episodes on systematic urinalysis were analyzed; 67.6% occurred in women, 41.9% in AML patients, 17.1% were bacteremic, 14.2% presented with UTS, and 61.9% were treated with short-course antibiotic treatment. One death was reported. In men, no relapse/recurrence was noted, even in the short-course antibiotic group. In women, 2.8% of episodes treated with short-course antibiotic led to relapse or recurrence. CONCLUSIONS: Relapse, recurrence, and mortality were uncommon events in FN patients experiencing bacteriuria episode, whatever the antibiotic duration. To distinguish asymptomatic bacteriuria from infection remained challenging in women. In men, systematic urinalysis at onset of FN could be useful.

Efficacy and Safety of Doravirine-Based Regimens in Real Life: A Prospective Monocentric French Study.

Doravirine (DOR) efficacy and safety have been evaluated in adult naive or treated patients starting a DOR-based regimen between September 15, 2019, and December 31, 2020. Medical history and examination, laboratory results, and tolerance were assessed during the 48 weeks of follow-up. Among the 77 patients included, virological control (VC) was noticed for 66 patients at baseline. Median age was 51 years, and 62% were men. The most common reason for initiating a DOR-based therapy was toxicity (44; 67%) and, especially, weight gain. A virological suppression (VS) was maintained in 55 (83%) patients of the VC group and noticed in 9 (82%) of the non-VC patients at week 48, by intention-to-treat analysis. On treatment analysis, 98% and 100% patients achieved VS in the VC and non-VC groups, respectively. The renal and metabolic tolerance were good. DOR-based regimens appear to be a safe and relevant strategy to circumvent drug interactions and drugs with a poor metabolic tolerance profile.

Risk factors for biliary stent infections in malignant biliary obstruction secondary to unresectable malignancies.

BACKGROUND: Palliative biliary drainage in patients with unresectable malignant biliary obstruction (MBO) frequently leads to biliary stent infection (BI), which could impact medical care. The aim of this study was to assess the risk factors for BI occurrence in patients after stenting procedure and the impact of BI on patient survival. METHODS: All consecutive patients hospitalized from 2014 to 2018 for MBO and biliary stenting were retrospectively included. Demographic, clinical, and microbiological characteristics of each BI episode during a 1-year follow-up were described. Documented BI was defined as the association of BI episode and confirmed blood stream infection (BSI). Univariate and multivariate analyses were performed to evaluate risk factors for the first BI occurrence. RESULTS: Among 180 patients, 56% were men (mean age of 69±12), and 54% have pancreatic cancer, 16% biliary cancer, 2% hepatic cancer, and 28% lymph node or metastatic compression; metallic stent was placed in 92%. A total of 113 BI episodes occurred in 74 patients, 55% of the first episodes occurring within 3 months after stenting. BI was documented in 56% of the episodes. Enterobacteriaceae were the most frequent pathogens found, while no yeasts were documented. Mortality rate in patients with BI was 64%. Multivariate analysis showed a significant difference in BI occurrence for two criteria: WHO score 3-4 (OR=8.79 [1.79-42.89]; p=0.007) and transpapillary stenting location (OR=3.72 [1.33-10.44]; p=0.013). CONCLUSION: Since transpapillary stenting is a risk factor for BI, preserving the papilla as much as possible is a priority so as to avoid BI.

Ulceroglandular Infection and Bacteremia Caused by Francisella salimarina in Immunocompromised Patient, France.

Although Francisella tularensis is a well-known, highly virulent bacterium that causes tularemia in humans, other Francisella species have been associated with sporadic human infections. We describe a human cutaneous infection with bacteremia caused by F. salimarina, a Francisella species recently identified from seawater and fishes, in an immunocompromised patient in France.

Late Onset of Chronic Granulomatous Disease Revealed by Paecilomyces lilacinus Cutaneous Infection.

Chronic granulomatous disease (CGD) is an inherited immunodeficiency due to defective leukocyte NADPH responsible for recurrent infections and aberrant inflammation. Mutations in the CYBB gene are responsible for the X-linked CGD and account for approximately 70% of the cases. CGD is diagnosed during childhood in males. Female carriers may have biased X-inactivation and may present with clinical manifestations depending on the level of residual NADPH oxidase activity. We report the case of a previously asymptomatic female carrier who was diagnosed at age 67 with a skin infection with the rare fungus Paecilomyces lilacinus as the first manifestation of CGD. Dihydrorhodamine 123 (DHR) activity was below 10%. Next-generation sequencing (NGS) revealed mutations in DNMT3A, ASXL1, and STAG2 suggesting that clonal hematopoiesis could be responsible for a progressive loss of NADPH oxidase activity and the late onset of X-linked CGD in this patient. Long-term follow-up of asymptomatic carrier women seems to be essential after 50 years old.

Efficacy of antibiotic short course for bloodstream infections in acute myeloid leukemia patients with febrile neutropenia: A retrospective comparative study.

OBJECTIVES: There is no specific recommendation about antimicrobial treatment length for documented infections in chemotherapy induced febrile neutropenia (FN). Practices have changed along time in our center regarding length of antibiotic treatment. The aim of this study was to compare long versus short antibiotic course for bloodstream infection (BSI) treatment in acute myeloid leukemia (AML) patients during FN. METHODS: This monocentric retrospective comparative study included all consecutive BSI episodes among AML patients with FN for 3 years (2017-2019). Episodes were classified regarding the length of antibiotic treatment, considered as short course if the treatment lasted ≤ 7 days, except for nonfermenting bacteria and Staphylococcus aureus or lugdunensis for which the threshold was ≤ 10 days and ≤ 14 days, respectively. The primary outcome was the number of BSI relapses in both groups within 30 days of antibiotic discontinuation. RESULTS: Among 71 AML patients, 104 BSI episodes were included; 48 (46%) received short course treatment. Only 8 (7.6%) BSI episodes relapsed within 30 days of antibiotic discontinuation, 5 having received short course treatment. No association was found between risk of relapse and short course of antibiotic treatment (p = 0.37). The only risk factor significantly associated with BSI relapse was neutropenia duration (p = 0.005). CONCLUSION: Antibiotic short course seemed as effective as prolonged treatment for BSI in AML patients during FN, with very few relapses at day 30. These encouraging findings should be confirmed through prospective studies.

Post-herpetic encephalitis cerebral abscess: Viral reactivation or latency site within central nervous system?

Herpetic encephalitis results from central nervous system invasion by herpes simplex virus. We report the case of a man who developed a cerebral abscess fifteen months after initial Herpetic encephalitis. Retrospectively, antiviral should not have been associated with antibiotics during abscess episode, as transcriptomic analysis reported no viral reactivation.

Chlorhexidine plus alcohol versus povidone iodine plus alcohol, combined or not with innovative devices, for prevention of short-term peripheral venous catheter infection and failure (CLEAN 3 study): an investigator-initiated, open-label, single centre, randomised-controlled, two-by-two factorial trial.

BACKGROUND: Two billion peripheral venous catheters are sold globally each year, but the optimal skin disinfection and types of devices are not well established. We aimed to show the superiority of disinfection with 2% chlorhexidine plus alcohol over 5% povidone iodine plus alcohol in preventing infectious complications, and of closed integrated catheters, positive displacement needleless-connectors, disinfecting caps, and single-use prefilled flush syringes used in combination (innovation group) over open catheters and three-way stopcocks for treatment administration (standard group) in preventing catheter failure. METHODS: We did an open-label, randomised-controlled trial with a two-by-two factorial design, for which we enrolled adults (age ≥18 years) visiting the emergency department at the Poitiers University Hospital, France, and requiring one peripheral venous catheter before admission to the medical wards. Before catheter insertion, patients were randomly assigned (1:1:1:1) using a secure web-based random-number generator to one of four treatment groups based on skin preparation and type of devices (innovative devices or standard devices; 2% chlorhexidine plus alcohol or 5% povidone iodine plus alcohol). Primary outcomes were the incidence of infectious complications (local infection, catheter colonisation, or bloodstream infections) and time between catheter insertion and catheter failure (occlusion, dislodgment, infiltration, phlebitis, or infection). This study is registered with ClinicalTrials.gov, NCT03757143. FINDINGS: 1000 patients were recruited between Jan 7, and Sept 6, 2019, of whom 500 were assigned to the chlorhexidine plus alcohol group and 500 to the povidone iodine plus alcohol group (250 with innovative solutions and 250 with standard devices in each antiseptic group). No significant interaction was found between the two study interventions. Local infections occurred less frequently with chlorhexidine plus alcohol than with povidone iodine plus alcohol (0 [0%] of 496 patients vs six [1%] of 493 patients) and the same was observed for catheter colonisation (4/431 [1%] vs 70/415 [17%] catheters among the catheters cultured; adjusted subdistribution hazard ratio 0·08 [95% CI 0·02-0·18]). Median time between catheter insertion and catheter failure was longer in the innovation group compared with the standard group (50·4 [IQR 29·6-69·4] h vs 30·0 [16·6-52·6] h; p=0·0017). Minor skin reactions occurred in nine (2%) patients in the chlorhexidine plus alcohol group and seven (1%) patients in the povidone iodine plus alcohol group. INTERPRETATION: For skin antisepsis, chlorhexidine plus alcohol provides greater protection of peripheral venous catheter-related infectious complications than does povidone iodine plus alcohol. Use of innovative devices extends the catheter complication-free dwell time. FUNDING: Becton Dickinson.

Trends in Antibiotic Consumption and Resistance in France Over 20 Years: Large and Continuous Efforts but Contrasting Results.

BACKGROUND: Antimicrobial resistance (AMR) is a serious threat to humanity. This paper describes the French efforts made since 2001 and presents data on antimicrobial consumption (AC) and AMR. METHODS: We gathered all data on AC and AMR recorded since 2001 from different national agencies, transferred on a regular basis to standardized European data on AC and resistance in both humans and animals. RESULTS: After a large information campaign implemented in France from 2001 to 2005 in humans, AC in the community decreased significantly (18% to 34% according to the calculation method used). It remained at the same level from 2005 to 2010 and increased again from 2010 to 2018 (8%). Contrasting results were observed for AMR. The resistance of Staphylococcus aureus decreased significantly. For gram-negative bacilli, the results were variable according to the microorganism. The resistance of Enterobacteriaceae to third-generation cephalosporins increased, remaining moderate for Escherichia coli (12% in 2017) but reaching 35% in the same year for Klebsiella pneumoniae. Resistance to carbapenems in those 2 microorganisms remained below 1%. Both global AC and resistance to most antibiotics decreased significantly in animals. CONCLUSIONS: Antibiotic consumption decreased significantly in France after a large public campaign from 2001 to 2005, but this positive effect was temporary. The effect on AMR varied according to the specific microorganism: The effect was very impressive for gram-positive cocci, variable for gram-negative bacilli, and moderate for E. coli, but that for K. pneumoniae was of concern. The consumption of and resistance to antibiotics decreased significantly in animals.

Why Methodology Is Important: Coffee as a Candidate Treatment for COVID-19?

BACKGROUND: During this pandemic situation, some studies have led to hasty conclusions about Corona Virus Disease-19 (COVID-19) treatment, due to a lack of methodology. This pedagogic study aimed to highlight potential biases in research on COVID-19 treatment. METHODS: We evaluate the effect of coffee's active part, 1,3,7-trimethylxanthine (TMX) on patients with COVID-19. A cohort of 93 patients, with a diagnosis of COVID-19 is analyzed. RESULTS: TMX group and control group included, respectively, 26 and 67 patients. In the TMX group, patients had a median length of stay in hospital of 5.5 days shorter than in the control group (9.5 vs. 15 days, p < 0.05). Patients in the control group were more severe than patients in the TMX group with a significantly higher National Early Warning Score 2 (NEWS-2 score) (8 vs. 6, p = 0.002). CONCLUSIONS: Multiple biases prevents us from concluding to an effect of coffee on COVID-19. Despite an important social pressure during this crisis, methodology and conscientiousness are the best way to avoid hasty conclusions that can be deleterious for patients. Identifier: NCT04395742.

Correction to: Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study.

The authors regret a mistake in Table 1.

Prevalence and Recovery From Olfactory and Gustatory Dysfunctions in Covid-19 Infection: A Prospective Multicenter Study.

BACKGROUND: Covid-19 is defined by an association of multiple symptoms, including frequently reported olfactory and gustatory disorders. OBJECTIVE: The main purpose of this study was to analyze the prevalence of these neurosensory impairments in patients with Covid-19, and to assess short-term recovery. METHODS: We performed a multicenter case series study during the Covid-19 epidemic. All patients presenting a RT-PCR-confirmed SARS-CoV-2 infection were included, whether hospitalized or treated at home. To analyze the prevalence and features of olfactory and gustatory dysfunctions, a phone interview was conducted 5 days after the positive PCR result. The questionnaire was submitted again 10 days later to patients having reported olfactory and gustatory disorders, in order to assess their recovery. RESULTS: 115 patients were included in our study. 81 patients (70%) reported olfactory and gustatory disorders without nasal obstruction or rhinorrhea. These impairments were more frequently reported in the female population, young people, and house-bound patients with mild symptomatic forms. Short-term recovery assessed at Day 15 was complete for 64% of the patients, and incomplete in 33%. Median recovery time was 15 days (4-27 days) after olfactory or gustatory symptom onset. CONCLUSION: Olfactory and gustatory dysfunctions related to Covid-19 are frequently reported and prevalent in mild symptomatic forms of the disease. Recovery in most cases seems rapid and complete.

Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study.

AIMS/HYPOTHESIS: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown. METHODS: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10-31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation. RESULTS: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th-75th percentile: 25.0-32.7) kg/m2; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin-angiotensin-aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA1c, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7. CONCLUSIONS/INTERPRETATIONS: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days. TRIAL REGISTRATION: clinicaltrials.gov NCT04324736.

Overcoming stability challenges during continuous intravenous administration of high-dose amoxicillin using portable elastomeric pumps.

While treatment of serious infectious diseases may require high-dose amoxicillin, continuous infusion may be limited by lack of knowledge regarding the chemical stability of the drug. Therefore, we have performed a comprehensive study so as to determine the chemical stability of high-dose amoxicillin solutions conducive to safe and effective continuous intravenous administration using portable elastomeric pumps. First, amoxicillin solubility in water was assessed within the range of 25 to 300 mg/mL. Then, amoxicillin solutions were prepared at different concentrations (25, 50, 125, 250 mg/mL) and stored in different conditions (5±2°C, 25±1°C, 30±1°C and 37±1°C) to investigate the influence of concentration and temperature on the chemical stability of amoxicillin. Finally, its stability was assessed under optimized conditions using a fully validated HPLC-UV stability-indicating method. Degradation products of amoxicillin were investigated by accurate mass determination using high-resolution mass spectrometry. Amoxicillin displayed limited water solubility requiring reconstitution at concentrations below or equal to 150 mg/mL. Amoxicillin degradation were time, temperature as well as concentration-dependent, resulting in short-term stability, in particular at high concentrations. Four degradation products of amoxicillin have been identified. Among them, amoxicilloic acid and diketopiperazine amoxicillin are at risk of allergic reaction and may accumulate in the patient. Optimized conditions allowing for continuous infusion of high-dose amoxicillin has been determined: amoxicillin should be reconstituted at 25 mg/mL and stored up to 12 hours at room temperature (22 ± 4°C) or up to 24 hours between 4 and 8°C.

Prognosis of Streptococcus pneumoniae endocarditis in France, a multicenter observational study (2000-2015).

BACKGROUND: Streptococcus pneumoniae is responsible for <2% of infective endocarditis (IE). The aim of this study was to assess the prognosis of pneumococcal IE. METHODS: This multicentric observational retrospective study included adult patients presenting with definite S. pneumoniae IE according to modified Dukes criteria from four French university hospitals over a 15-year period, January 2000-December 2015. Survival rate at 90 days and 2 years after diagnosis, appropriateness of antibiotherapy, and pneumococcal vaccination status were determined. Risk factors for mortality were studied by univariate analysis. RESULTS: Of 3886 patients admitted with IE during the study period, 50 (1.3%) had pneumococcal IE, mostly males (n = 38, 76%), with a mean age of 60 ±â€¯14 years. Predisposing conditions for IE or for invasive pneumococcal disease (IPD) involved 24% and 78% of the cases, respectively. Only 2 patients were vaccinated against pneumococcus before IE and 13 (26%) after IE. Antimicrobial strategy was in accordance with the 2015 ESC Guidelines in 28%. Cardiac surgery was performed in 56%, and was associated with better survival (p = 0.012). In the 40 patients followed until 2 years, the survival rate was 67%, deaths occurring mostly before 90 days. Age ≥ 65 was a risk factor for mortality (p = 0.011). CONCLUSION: Pneumococcal IE remains rare but with a poor prognosis. Resort to surgery is yet to be determined. Predisposing conditions for IPD are the main factors leading to pneumococcal IE. They could be prevented by vaccine coverage improvement.

Thrombosis and antiphospholipid antibody syndrome during acute Q fever: A cross-sectional study.

Q fever is a neglected and potentially fatal disease. During acute Q fever, antiphospholipid antibodies are very prevalent and have been associated with fever, thrombocytopenia, acquired heart valve disease, and progression to chronic endocarditis. However, thrombosis, the main clinical criterion of the 2006 updated classification of the antiphospholipid syndrome, has not been assessed in this context. To test whether thrombosis is associated with antiphospholipid antibodies and whether the criteria for antiphospholipid syndrome can be met in patients with acute Q fever, we conducted a cross-sectional study at the French National Referral Center for Q fever.Patients included were diagnosed with acute Q fever in our Center between January 2007 and December 2015. Each patient's history and clinical characteristics were recorded with a standardized questionnaire. Predictive factors associated with thrombosis were assessed using a rare events logistic regression model. IgG anticardiolipin antibodies (IgG aCL) assessed by an enzyme-linked immunosorbent assay were tested on the Q fever diagnostic serum. A dose-dependent relationship between IgG aCL levels and thrombosis was tested using a receiver operating characteristic (ROC) analysis.Of the 664 patients identified for inclusion in the study, 313 (47.1%) had positive IgG aCL and 13 (1.9%) were diagnosed with thrombosis. Three patients fulfilled the antiphospholipid syndrome criteria. After multiple adjustments, only positive IgG aCL (relative risk, 14.46 [1.85-113.14], P = .011) were independently associated with thrombosis. ROC analysis identified a dose-dependent relationship between IgG aCL levels and occurrence of thrombosis (area under curve, 0.83, 95%CI [0.73-0.93], P < .001).During acute Q fever, antiphospholipid antibodies are associated with thrombosis, thrombocytopenia, and acquired valvular heart disease. Antiphospholipid antibodies should be systematically assessed in acute Q fever patients. Hydroxychloroquine, which has been previously shown to antagonize IgG aCL pathogenic properties, should be tested in acute Q fever patients with anticardiolipin antibodies to prevent antiphospholipid-associated complications.Key Point: In addition to fever, thrombocytopenia and acquired valvular heart disease, antiphospholipid antibodies are associated with thrombosis during acute Q fever.